ICS Institute of Neuropathology

Barcelona, Spain

ICS Institute of Neuropathology

Barcelona, Spain
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Beyer K.,Hospital Universitario Germans Trias i Pujol | Beyer K.,ICS Institute of Neuropathology | Domingo-Sabat M.,Hospital Universitario Germans Trias i Pujol | Santos C.,Autonomous University of Barcelona | And 4 more authors.
Brain | Year: 2010

Lewy body diseases include dementia with Lewy bodies and Parkinson's disease. Whereas dementia with Lewy bodies and Parkinson's disease can be distinguished as separate clinical entities, the pathological picture is very often identical, α-synuclein aggregation is a key event in the pathogenesis of Lewy body diseases and β-synuclein inhibits α-synuclein aggregation in vitro and in vivo. Recently, β-synuclein has been shown to interact directly with α-synuclein, regulating its functionality and preventing its oligomerization. In this study, we analysed the expression of two β-synuclein transcript variants and the main α-synuclein transcript SNCA140, in frozen samples of three areas from brains of patients with (i) pure diffuse Lewy body pathology; (ii) pure Alzheimer's disease pathology; (iii) diffuse Lewy body pathology and concomitant Alzheimer's disease pathology and (iv) controls. Relative messenger RNA expression was determined by real-time polymerase chain reaction, expression changes were evaluated by the ΔΔCt method and messenger RNA expression data were confirmed at the protein level. A drastic diminution of β-synuclein expression was observed in cortical areas of all samples that presented neuropathological features corresponding to pure diffuse Lewy body pathology and the clinical phenotype of dementia with Lewy bodies, but not in those with neuropathological features corresponding to diffuse Lewy body pathology and concomitant Alzheimer's disease pathology or the clinical phenotype of Parkinson's disease with dementia. The correlation of expression data with the clinical phenotype and neuropathological diagnosis of the patients suggested the existence of a specific molecular subtype of dementia with Lewy bodies, characterized by a strong decrease of β-synuclein in the frontal and temporal cortices. Furthermore, our findings provide new insights into the pathogenesis of Lewy body diseases that may be important for the understanding of molecular mechanisms involved in these complex diseases. © 2010 The Author. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.


Beyer K.,Autonomous University of Barcelona | Beyer K.,ICS Institute of Neuropathology | Ispierto L.,Autonomous University of Barcelona | Latorre P.,Autonomous University of Barcelona | And 3 more authors.
Journal of the Neurological Sciences | Year: 2011

Parkinson disease (PD) is the most important movement disorder and about 50% of patients develop dementia over the time. PD belongs to the group of Lewy body disorders. Alpha-synuclein (AS) is the main component of Lewy bodies and its aggregation is a key event in the pathogenesis of PD. Beta-synuclein (BS) inhibits AS aggregation in vitro and in vivo and has been shown to interact directly with AS regulating its functionality and preventing its oligomerization. Recently, we have described a molecular subgroup of DLB characterized by the drastic BS reduction in cortical areas. In this study we have analyzed the expression of two BS transcripts and the main AS transcript SNCA140, in frozen samples of three brain areas, temporal cortex, caudate nucleus and pons, from patients with PD and PDD in comparison with controls. Relative mRNA expression was determined by real-time PCR with SybrGreen, neuron-specific-enolase as housekeeping gene and the deltadeltaCt method. The most important difference in BS and AS mRNA expression between PD and PDD was found in the caudate nucleus, where BS mRNA was overexpressed in PD and AS mRNA diminished in PDD. Our findings provide new insights into the pathogenesis of dementia in PD, indicating that differential BS and AS expression in the caudate nucleus may represent one of the molecular mechanisms involved in these complex diseases. © 2011 Elsevier B.V.

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